Raman spectroscopy is a known optical technique for identifying molecules. The identification is based on vibrational information specific to chemical bonds and symmetry of molecules. The technique provides a fingerprint by which molecules may be uniquely identified. Consequently, Raman spectroscopy can be used as a qualification and quantification technique for detecting analytes of interest in a sample.
As optical, non-destructive technique, Raman spectroscopy also be used for identifying targets of interest in medical applications, for example identifying molecules in the skin of an individual and to estimate the total number of such molecules in the volume probed. One application that has been envisaged in the past is the sensing of glucose in a living creature.
Nevertheless, as for most optical techniques, the response signal when measuring glucose is very limited. To monitor glucose in a living creature, a small signal variation is to be measured while a significant amount of background signal is present. Therefore it is important that a detector based on Raman spectroscopy has a high sensitivity.
Raman scattering will lead to a light signal that is isotropic, i.e. emitting in all directions. The spectrometer needs to capture light propagating in all angles as much as possible. In addition, since light scatters readily in skin, the light that is available at the skin surface is spread out over a substantial area (1 mm2 or more, depending on the illumination scheme used). This creates the challenge of collecting light over all angles and a large area, i.e. a large étendue (proportional to area times solid angle), which is a fundamental challenge in optics since spectrometers that are able to collect and process a light signal with a large étendue are challenging to design and build.
Moreover due to the differences in the local geometry of the skin (e.g. different thicknesses and microstructure of the various layers that make up skin) for different positions on the skin as well as for different individuals, it is difficult to quantify the concentration of a particular analyte without performing calibration steps for each individual separately. Therefore, to obtain a reproducible technique, calibration is performed systematically. This is typically a time consuming and cumbersome process that limits the applicability of the Raman technique for doing accurate routine non-invasive measurements of important analytes such as glucose, cholesterol, ethanol, etc.
Together with the required high sensitivity and the need for calibration, another requirement typically is the ease of use of the sensor for the user. For example in case of glucose sensing, sensing typically needs to be performed at least a couple of times a day. Conventional Raman systems typically are large optical systems and cannot be used for convenient day-to-day glucose monitoring. Efforts have been made to miniaturize optical Raman systems. Some suggestions have been made in the past to use an implantable sensor, an example thereof being described in U.S. patent application Ser. No. 13/415,392. Whereas implantable sensors can be easy to use and even allow continuous monitoring once they have been implanted, such implantable sensors require accurate packaging while maintaining access to the tissue or fluids to be measured and also require a surgical step for implanting them.
There is still a need for a good Raman based optical sensor, with high sensitivity, good accuracy and with good ease of use for the user.